Project Summary Oxidative substrate functionalization provides the opportunity to introduce new chemical functionality and structural complexity. Synthetic electrocatalysis provides a conceptual platform for sustainable oxidation technologies by obviating the need for stoichiometric chemical oxidants, and the attendant waste implied by these reagents. In practice, slow interfacial electron transfer chemistry of many organic molecules prevents widespread application of electrochemical methods to fine-chemical synthesis. Further, single electron-transfer processes, which are the currency of electrochemical strategies, are not common elementary steps in synthetically important transformations. The central hypothesis of this proposal is that development of hypervalent iodine electrocatalysis will provide a platform to achieve a broad array of oxidative substrate functionalization electrochemically. This hypothesis is predicated on the rich chemistry of hypervalent iodine reagents, which are well-known to participate in selective two-electron oxygenation, amination, halogenation, and hydrocarbyl transfer reactions. Successful development of hypervalent iodine electrocatalysis would substantially impact the synthesis of fine chemicals, such as molecular therapeutics. This proposal aims to first develop electrocatalysis via electrochemically generated hypervalent iodine species. Specifically, the proposed strategy leverages a previously unappreciated strategy for the synthesis of hypervalent iodine species ? that one-electron pathways provide efficient access to selective two-electron chemical oxidants based on hypervalent iodine compounds ? to develop synthetic hypervalent iodine electrocatalysis. Preliminary data indicate that electrochemically generated carboxy radicals enable facile electrosynthesis of hypervalent iodine species and that electrochemically generated hypervalent iodine species are competent mediators of oxidative C?H / N?H coupling. We propose to extend these preliminary results to develop new synthetically useful transformations, such as oxidative C?H functionalization. Further, the fundamental understanding of the elementary steps involved in the oxidation of aryl iodides provides the chemical insight necessary to develop novel methods of hypervalent iodine synthesis that will substantially expand the synthetic scope of hypervalent iodine catalyzed substrate oxidation. A long-term goal of these efforts is to identify new catalyst scaffolds to enable catalyst-controlled site- and stereoselective C?H functionalization which would provide direct access to complex molecular architectures functionalized at positions of metabolic consequence, which would impact the evaluation of drug metabolites and impact the discovery of new therapeutics. Together, the proposed research efforts will provide both new sustainable synthetic methods and expand the synthetic toolbox of transformations that are available for the synthesis of functional molecules. !